The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.
The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes
Open accessAbstract
Transcriptional enhancers function as docking platforms for combinations of transcription factors (TFs) to control gene expression. How enhancer sequences determine nucleosome occupancy, TF recruitment and transcriptional activation in vivo remains unclear. Using ATAC-seq across a panel of Drosophila inbred strains, we found that SNPs affecting binding sites of the TF Grainy head (Grh) causally determine the accessibility of epithelial enhancers. We show that deletion and ectopic expression of Grh cause loss and gain of DNA accessibility, respectively. However, although Grh binding is necessary for enhancer accessibility, it is insufficient to activate enhancers. Finally, we show that human Grh homologs-GRHL1, GRHL2 and GRHL3-function similarly. We conclude that Grh binding is necessary and sufficient for the opening of epithelial enhancers but not for their activation. Our data support a model positing that complex spatiotemporal expression patterns are controlled by regulatory hierarchies in which pioneer factors, such as Grh, establish tissue-specific accessible chromatin landscapes upon which other factors can act.
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“Thus, a potentially large fraction of accessible regions, as captured by scATAC-seq, may not represent functional enhancers.”
From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [9]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The mechanisms of pioneer factor action are still being established [37], but at least some of them (such as FOXA, OCT4 and SOX2/SOX11) have been shown to initiate chromatin opening by direct displacement of histones [38–41], whilst many others recruit chromatin remodelers [42–50].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [41]
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“However, chromatin accessibility is not necessarily always associated with enhancer activity35.”
From Single-cell spatial multi-omics and deep learning dissect enhancer-driven gene regulatory networks in liver zonation (2024) · cites this paper as [35]
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“chromatin accessibility is necessary but not sufficient for activity9.”
From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [9]
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“chromatin accessibility is not necessarily always associated with enhancer activity9.”
From Enhancer grammar of liver cell types and hepatocyte zonation states (2022) · cites this paper as [9]
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Cites
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106
Scikit-learn: Machine Learning in Python
Pedregosa, F., Varoquaux, G., Gramfort, A., Michel, V., Thirion, B., Grisel, O., Blondel, M., Müller, A., Nothman, J., Louppe, G., et al. (2012) · arXiv · doi:10.48550/arxiv.1201.0490 · Cited by 71,016
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
Fast gapped-read alignment with Bowtie 2
Langmead, B., & Salzberg, S. L. (2012) · Nature Methods · doi:10.1038/nmeth.1923 · Cited by 56,400
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625
featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219
Model-based Analysis of ChIP-Seq (MACS)
Zhang, Y., Liu, T., Meyer, C. A., Eeckhoute, J., Johnson, D. S., Bernstein, B. E., Nusbaum, C., Myers, R. M., Brown, M., Li, W., et al. (2008) · Genome Biology · doi:10.1186/gb-2008-9-9-r137 · Cited by 18,386
An integrated encyclopedia of DNA elements in the human genome
The ENCODE Project Consortium (2012) · Nature · doi:10.1038/nature11247 · Cited by 18,072
The variant call format and VCFtools
Danecek, P., Auton, A., Abecasis, G. R., Albers, C. A., Banks, E., DePristo, M. A., Handsaker, R. E., Lunter, G. A., Marth, G., Sherry, S. T., et al. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr330 · Cited by 16,450
pROC: an open-source package for R and S+ to analyze and compare ROC curves
Robin, X., Turck, N., Hainard, A., Tiberti, N., Lisacek, F., Sanchez, J.-C., & Müller, M. (2011) · BMC Bioinformatics · doi:10.1186/1471-2105-12-77 · Cited by 13,697
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Sorted by citations
Pioneer Transcription Factors Initiating Gene Network Changes
Zaret, K. S. (2020) · Annual Review of Genetics · doi:10.1146/annurev-genet-030220-015007 · Cited by 409
Ulz, P., Perakis, S. O., Zhou, Q. X., Moser, T., Belic, J., Lazzeri, I., Wölfler, A., Zebisch, A., Gerger, A., Pristauz, G., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-12714-4 · Cited by 264
Pioneer factors as master regulators of the epigenome and cell fate
Balsalobre, A., & Drouin, J. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-022-00464-z · Cited by 251
Chromatin accessibility profiling methods
Minnoye, L., Marinov, G. K., Krausgruber, T., Pan, L., Marand, A. P., Secchia, S., Greenleaf, W. J., Furlong, E. E. M., Zhao, K., Schmitz, R. J., et al. (2021) · Nature Reviews Methods Primers · doi:10.1038/s43586-020-00008-9 · Cited by 206
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Metadata
- Authors
- Jacobs, J., Atkins, M., Davie, K., Imrichova, H., Romanelli, L., Christiaens, V., Hulselmans, G., Potier, D., Wouters, J., Taskiran, I. I., Paciello, G., González-Blas, C. B., Koldere, D., Aibar, S., Halder, G., & Aerts, S.
- Affiliations
- VIB-KU Leuven Center for Brain & Disease Research (BE)
- VIB-KU Leuven Center for Cancer Biology (BE)
- Boğaziçi University (TR)
- Politecnico di Torino (IT)
- Corresponding author
- Aerts, Stein
- ORCID
- Venue
- Nature Genetics
- Published
- 2018-06-04
- Volume
- 50
- Issue
- 7
- Pages
- 1011-1020
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- PMC
- PMC6031307
- OpenAlex
- W2806844404
- Cited by
- 155
- References
- 98
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 22 · 2023: 15 · 2022: 23 · 2021: 17 · 2020: 28 · 2019: 16 · 2018: 8
- FWCI
- 6.14
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Lirias (submittedVersion, other-oa)
- Funders
- National Institutes of Health (P40OD018537)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- transcription factors, enhancer accessibility, nucleosome displacement, pioneer factors, chromatin accessibility, GRHL1, GRHL2, GRHL3, Drosophila, transcriptional activation, regulatory hierarchy, tissue-specific gene expression, single nucleotide polymorphisms
- MeSH terms
- Animals, Binding Sites, Chromatin, DNA-Binding Proteins, Drosophila melanogaster, Enhancer Elements, Genetic, Epithelial Cells, Humans, Nucleosomes, Transcription Factors, Transcriptional Activation, Gene Expression Regulation, Developmental, Polymorphism, Single Nucleotide, Drosophila Proteins, Animals, Genetically Modified, Cell Line, Tumor, MCF-7 Cells
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